Decreased Lamin B1 Levels Affect Gene Positioning and Expression in Postmitotic Neurons

• Published in: Neuroscience research Vol. 173; pp. 22 - 33
• Main Authors: Noguchi, Azumi, Ito, Kenji, Uosaki, Yuichi, Ideta-Otsuka, Maky, Igarashi, Katsuhide, Nakashima, Hideyuki, Kakizaki, Toshikazu, Kaneda, Ruri, Uosaki, Hideki, Yanagawa, Yuchio, Nakashima, Kinichi, Arakawa, Hirokazu, Takizawa, Takumi
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2021
• Subjects: Animals; Cell Nucleus; chromatin; gene expression; gene positioning; Humans; Lamin Type B - genetics; maturation; Mice; Neurogenesis; neuron; Neurons; nuclear lamina; neuron; nuclear lamina; maturation; chromatin; gene positioning; gene expression
• ISSN: 0168-0102; 1872-8111; 1872-8111
• DOI: 10.1016/j.neures.2021.05.011

•Genes in mouse 14qD2 locus are upregulated during maturation of hippocampal neurons.•They are relocated away from the nuclear periphery during neuronal maturation.•Decreased lamin B1 plays a role in relocation and transcription of the 14qD2 locus.•Overexpression of lamin B1 in neurons repressed transcription of the Egr3 gene.•Reduced lamin B1 may be crucial for chromatin organization in postmitotic neurons. Gene expression programs and concomitant chromatin regulation change dramatically during the maturation of postmitotic neurons. Subnuclear positioning of gene loci is relevant to transcriptional regulation. However, little is known about subnuclear genome positioning in neuronal maturation. Using cultured murine hippocampal neurons, we found genomic locus 14qD2 to be enriched with genes that are upregulated during neuronal maturation. Reportedly, the locus is homologous to human 8p21.3, which has been extensively studied in neuropsychiatry and neurodegenerative diseases. Mapping of the 14qD2 locus in the nucleus revealed that it was relocated from the nuclear periphery to the interior. Moreover, we found a concomitant decrease in lamin B1 expression. Overexpression of lamin B1 in neurons using a lentiviral vector prevented the relocation of the 14qD2 locus and repressed the transcription of the Egr3 gene on this locus. Taken together, our results suggest that reduced lamin B1 expression during the maturation of neurons is important for appropriate subnuclear positioning of the genome and transcriptional programs.